Bibliographic details of the publications numerically referred to in this specification are collected at the end of the description. Sequence Identity Numbers (SEQ ID NOs.) for the nucleotide and amino acid sequences referred to in the specification are defined following the bibliography.
Throughout this specification, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising”, will be understood to imply the inclusion of a stated element or integer or group of elements or integers but not the exclusion of any other element or integer or group of elements or integers.
The meat industry in Australia and, indeed, in most countries of the world, is an important aspect of the overall livestock industry. However, the meat industry is subject to rapid economic downturn in response to disease conditions affecting the animals as well as human diseases putatively carried by the animals. It is important, therefore, to have well defined treatment, prophylactic and diagnostic procedures available to deal with infections or potential infections in animals and humans.
Pigs form a major component of the meat industry. However, pigs are sensitive to a wide spectrum of intestinal diseases collectively referred to as porcine proliferative enteropathy (PPE). This disease has previously been known as intestinal adentomatosis complex (1), porcine intestinal adenomatosis (PIA), necrotic enteritis (2), proliferative haemorrhagic enteropathy (3), regional ileitis (4), haemorrhagic bowel syndrome (5), porcine proliferative enteritis and Campylobacter spp induced enteritis (6).
There are two main forms of PPE: a non-haemorrhagic form represented by intestinal adenomatosis which frequently causes growth retardation and mild diarrhoea; and a haemorrhagic form, which is often fatal, represented by proliferative haemorrhagic enteropathy (PHE) where the distal small intestine lumen becomes engorged with blood. PPE has been reported in a number of animal species including pigs (14), hamsters (7), ferrets (15), guinea pigs (16), rabbits (17) as well as avian species (18).
The causative organism of PPE is a Campylobacter-like organism referred to herein as “Lawsonia intracellularis” (26). The organism has also been previously referred to as Ileal symbiont intracellularis (7). PPE-like diseases in pigs may also be caused by other pathogens such as various species of Campylobacter (8).
Lawsonia intracellularis is an intracellular, possibly obligate intracellular, bacterium. It can only be cultured in vitro with tissue culture cells (9, 26). Pigs suffering from PPE are characterised by multiple abnormal immature crypts and L. intracellularis is located in the cytoplasm of these crypt cells.
PPE is a significant cost component associated with the pig industry, especially in terms of stock losses, medication costs, reduced growth rates of pigs and increased feed costs. PPE also contributes to downstream indirect costs in, for example, additional labour costs and environmental costs in dealing with antibiotic residue contamination and in control measures to prevent the organism being passed on or carried to other animals or humans.
Current control strategies for PPE rely on the use of antibiotics. However, such a strategy is considered to be short to medium term especially as governmental regulatory pressures tend to target animal husbandry practices which are only supported by prophylactic antibiotics. There is a need, therefore, to develop effective, safe and low cost alternatives to the use of antibiotics. There is also a need to extend this alternative to antibiotics to similar organisms which infect other animals such as humans.
In work leading up to the present invention, the inventors sought to develop vaccines for the prophylaxis and treatment of PPE in animals and birds. The vaccines of the present invention provide an efficacious alternative to the use of antibiotics with a range of consequential husbandry and medical benefits.